An external atmospheric pressure electrospray ionization source and electrostatic lenses for ion transport have been designed, constructed and tested for an ion cyclotron resonance spectrometer. Ions formed at atmospheric pressure have been transmitted into an analyzer cell region, with the resulting demonstration of high mass resolution for both thermally ionized and electrosprayed ions. Improvements in the electrospray source as well as the transport ion optics are in progress, so that the resulting system can be used to measure the molecular weights of proteins and DNA fragments. Derivatization chemistry and separation conditions suitable for the detection of acidic tryptophan metabolites generated in cultured cell or tissue incubation experiments have been demonstrated using liquid chromatography-particle beam-negative chemical ionization mass spectrometry. A new derivatization reagent (pentafluorophenyl boronic acid) has been tested for use in forming cyclic boronates of glycols for improved detection in gas chromatography-mass spectrometry. Organic ion imaging using tandem mass spectrometry has been demonstrated to produce spatially resolved mass selective images, representing a new type of molecular or chemical microscopy.